The present invention relates to a transformed epithelial cell line that maintains the abnormal ion transport characteristics of cystic fibrosis while extending the proliferation capability beyond that of a primary epithelial cell culture. Moreover it relates to the testing of putative therapeutic compounds on such transformed cells as well as to applying genetic complementation analysis of candidate cystic fibrosis genes on such transformed cells.
Cystic fibrosis (CF) is an autosomal recessive disease that affects epithelia of the airways, sweat glands, pancreas, and other organs. Abnormal regulation of transport proteins in the apical cell membrane, including the conductive Cl.sup.- channel, is the direct effect of the abnormal gene.
There is a pressing need to develop treatments for CF. Based on what is presently known of the biochemical effects resulting from the genetic defect it may be possible to find compounds that are able to ameliorate the effects of the disease. In the case of many physiological defects therapeutic drugs have been identified using isolated cells for rapid mass screening of candidate drugs. Therefore it would be ideal to have such a screening system for CF.
CF abnormalities are exhibited in primary cultures of CF epithelial cells however the difficulties associated with obtaining tissue and with growing isolated cells from the tissue currently restricts the approach described above. A number of other human epithelial cell types have previously been transformed by SV40T genes in attempts to enhance the growth potential of the cell line including human bronchial epithelial cells (Reddel et al., Cancer Research 48, 1904-1909, 1988). The epithelial cell line of this invention with its expanded growth potential increases the availability of phenotypic cystic fibrosis cells making possible screening of putative therapeutic drugs and analysis of cystic fibrosis genes.